State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Front Immunol. 2022 Jun 10;13:859806. doi: 10.3389/fimmu.2022.859806. eCollection 2022.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease worldwide. Infiltration of pro-inflammatory macrophages (M1 macrophages) contributes to the occurrence of bowel inflammation. Transplantation of mesenchymal stem cells (MSCs) is a promising therapeutic strategy for UC, but the exact mechanism remains unknow yet. Here, we treated DSS-induced colitis mice with adipose-derived mesenchymal stem cells (ADMSCs) and revealed that ADMSCs alleviated colon inflammation by reducing the infiltration of M1 macrophages. Moreover, ADMSCs exerted this therapeutic effect by inhibiting succinate accumulation, increasing PHD2 to prevent M1 macrophages from overexpressing HIF-1α and thereby reprogramming the glycolytic pathway of M1 macrophages. Meanwhile, the succinate secreted by M1 macrophages triggered ADMSCs to secrete PGE2 in return, which could also shift macrophages from M1 phenotype to M2. Our work demonstrated an immunomodulatory effect of ADMSCs and provided a novel perspective on UC therapy.
溃疡性结肠炎（UC）是一种全球性的慢性炎症性肠病。促炎巨噬细胞（M1 巨噬细胞）的浸润导致肠道炎症的发生。间充质干细胞（MSCs）的移植是 UC 的一种有前途的治疗策略，但确切的机制尚不清楚。在这里，我们用脂肪间充质干细胞（ADMSCs）治疗 DSS 诱导的结肠炎小鼠，发现 ADMSCs 通过减少 M1 巨噬细胞的浸润来减轻结肠炎症。此外，ADMSCs 通过抑制琥珀酸积累，增加 PHD2 来防止 M1 巨噬细胞过度表达 HIF-1α，从而重编程 M1 巨噬细胞的糖酵解途径，发挥这种治疗作用。同时，M1 巨噬细胞分泌的琥珀酸反过来触发 ADMSCs 分泌 PGE2，也可以使巨噬细胞从 M1 表型向 M2 表型转变。我们的工作证明了 ADMSCs 的免疫调节作用，并为 UC 的治疗提供了新的视角。
